PROJECT SUMMARY Competitive Revision to P41 EB017183 The Center for Advanced Imaging Innovation and Research (CAI2R) pursues a mission of bringing people together to create new ways of seeing. The work of our Center has been focused on creating new paradigms for the acquisition, reconstruction, and interpretation of biomedical images, and on implementing new collaboration models in order to translate these developments rapidly into clinical practice. In the proposed Competitive Revision, we will apply our experience in working with biomedical images and other signals to a new collaboration, aimed at the urgent need for COVID-19 testing. Parent Grant Summary The world of biomedical imaging is changing, and CAI2R has been at the forefront of that change. Tasks that were once the sole domain of meticulously-engineered imaging hardware are now beginning to be accomplished in software, increasingly informed by diverse arrays of inexpensive auxiliary sensors. Information once pursued through the laborious acquisition of carefully separated image datasets is now being derived from newly integrated, and richly quantitative, data streams. In keeping with these themes, our Center will be organized around the following four Technology Research and Development (TR&D) projects going forward: 1. Reimagining the Future of Scanning: Intelligent image acquisition, reconstruction, and analysis. 2. Unshackling the Scanners of the Future: Flexible, self-correcting, multisensor machines. 3. Enriching the Data Stream: MRI and PET in concert. 4. Revealing Microstructure: Biophysical modeling and validation for discovery and clinical care. Competitive Revision Summary With the appearance of COVID-19, the world changed suddenly. The need for definitive but also broadly available COVID-19 testing is clear, and is identified as a top priority in the Notice of Special Interest (NOT-EB- 20-008) to which this proposal responds. In this project, we will partner with colleagues in chemical engineering and virology to develop, evaluate, and deploy a new electrochemical device for multifaceted point- of-care or home-based COVID-19 testing. The device will use molecular surface imprinting to create a gold surface sensitive to SARS-CoV-2 spike proteins and other analytes of interest. Sensitive solid-state electronics will then detect the presence of these analytes in patient samples, ultimately allowing rapid and simultaneous assessment of COVID-19 infection, immunity and severity. Specific Aims of the Competitive Revision are as follows: 1. Prototype. We will test whether a COVID-19 signal may already be obtained using our best current imprinting methods and electronic detection circuitry. 2. Characterize. We will use biobanked patient samples to establish sensitivity, specificity, and limits of detection (LOD) of our initial prototype for COVID-19, as opposed to other common viruses. 3. Optimize and iterate. Informed by Aims 1 and 2, we will develop optimized electronics, surface imprinting protocols, and measurement strategies to improve sensitivity and specificity. 4. Evaluate and distribute. We will test designs with promising performance prospectively in a cohort of subjects presenting for testing at NYU, and will compare results with standard RT-PCR COVID-19 testing, with an eye towards FDA approval, commercialization, and broader distribution.